SARS-CoV-2 evolved variants optimize binding to cellular glycocalyx.
ACE2
Brownian dynamics
COVID-19
SARS-CoV-2
biomimetic
biosensor
electrostatic potential
heparan sulfate
heparin
lateral-flow assay
spike
Journal
Cell reports. Physical science
ISSN: 2666-3864
Titre abrégé: Cell Rep Phys Sci
Pays: United States
ID NLM: 101769239
Informations de publication
Date de publication:
19 Apr 2023
19 Apr 2023
Historique:
received:
08
11
2022
revised:
07
02
2023
accepted:
07
03
2023
medline:
20
4
2023
pubmed:
20
4
2023
entrez:
20
04
2023
Statut:
ppublish
Résumé
Viral variants of concern continue to arise for SARS-CoV-2, potentially impacting both methods for detection and mechanisms of action. Here, we investigate the effect of an evolving spike positive charge in SARS-CoV-2 variants and subsequent interactions with heparan sulfate and the angiotensin converting enzyme 2 (ACE2) in the glycocalyx. We show that the positively charged Omicron variant evolved enhanced binding rates to the negatively charged glycocalyx. Moreover, we discover that while the Omicron spike-ACE2 affinity is comparable to that of the Delta variant, the Omicron spike interactions with heparan sulfate are significantly enhanced, giving rise to a ternary complex of spike-heparan sulfate-ACE2 with a large proportion of double-bound and triple-bound ACE2. Our findings suggest that SARS-CoV-2 variants evolve to be more dependent on heparan sulfate in viral attachment and infection. This discovery enables us to engineer a second-generation lateral-flow test strip that harnesses both heparin and ACE2 to reliably detect all variants of concern, including Omicron.
Identifiants
pubmed: 37077408
doi: 10.1016/j.xcrp.2023.101346
pii: S2666-3864(23)00111-X
pmc: PMC10080732
doi:
Types de publication
Journal Article
Langues
eng
Pagination
101346Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM132826
Pays : United States
Organisme : NIBIB NIH HHS
ID : T32 EB009380
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI171954
Pays : United States
Informations de copyright
© 2023 The Author(s).
Déclaration de conflit d'intérêts
The authors declare the following patent: Glycosaminoglycan articles and methods relating thereof. Inventors: S.H.K, R.F. Application number PCT/US22/79641 was submitted on this work.
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